Background: Pyrimidinones and its derivatives are present in many anti-cancer agents, it has been reported that these substances were proven to have significant activities against different types of human cancers. The incorporation of [1,2,3]-triazole, a nitrogen rich unit not only increases the efficacy but also increases lipophilicity of the drug molecule. As our research to synthesize newer molecules of effective cytotoxicity, we focused on pyrimidinone and [1,2,3]-triazoles systems, as important scaffolds with the expectation of potential cytotoxic properties. Methods: Novel series of [1,2,3]-triazole carboxamides (5a-j) were synthesized starting from 3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. Structure of all the synthesized compounds were elucidated based on IR, 1H-NMR, 13C-NMR and LC-MS data. Compounds were focused for their in vitro cytotoxicity against A375 melanoma cancer cell lines, MDA-MB-231 breast cancer cell lines and HEK 293-Human embryonic kidney cell lines using colorimertic MTT assay. The potent compound was evaluated for DNA binding studies. Results: Most of the Pyrimidinone conjugated [1,2,3]-triazole carboxamides found to be selective towards melanoma cancer cell lines than breast cancer cell lines. Compounds 5d, 5i and 5b were effective against A375 cancer cell lines and are found to be non-toxic against HEK 293-Human embryonic kidney cell lines. The potent compound 5d showed good intrinsic binding constant (Kb) value 3.12 x 103 M-1 in UV based DNA titration. Conclusion: Newly synthesized pyrimidinone conjugated 1,2,3-triazole carboxamide derivatives showed the significant cytotoxicity and the potent compound showed good intrinsic binding constant in UV based DNA titration.